Caring for sepsis survivors

An 81-year-old man with hypertension and type 2 diabetes mellitus is hospitalized with
Klebsiella urinary tract infection, bacteremia, acute renal injury, and lactic acidosis. Fluid
and antibiotic therapy normalize his creatinine and lactic acid levels, vital signs,
and blood pressure. He does not need physical restraints, a central line, or an indwelling
urinary catheter. While preparing for discharge, he asks about his long-term prognosis.

Photo by Thinkstock.

The treating hospitalist faces the issue of postsepsis sequelae—a syndrome
of late mortality, functional and cognitive impairment, and mental health problems
affecting the increasing number of patients who survive severe sepsis or septic shock.

“I see a lot of [sepsis survivors] with cognitive impairment—cloudy
thinking or difficulty completing tasks—in addition to weakness or exercise
limitations and recurrent sepsis or infection,” said ACP Member Hallie Prescott,
MD, MSc, a medical intensivist at the University of Michigan and Veterans Affairs
Hospital in Ann Arbor.

In another study of national data, published in the March 10, 2015, JAMA, more than 40% of patients who survived severe sepsis were rehospitalized within 90 days. They were significantly more likely to be readmitted with recurrent
sepsis, congestive heart failure, acute renal failure, or respiratory failure compared
to similar patients who had not had sepsis. Dr. Prescott was a coauthor on both of
these studies.

Additional research has linked sepsis to long-term mortality, increased health care
utilization, new and often severe cognitive and functional impairments, lower quality
of life, and increased rates of admission to long-term care facilities.

The problem doesn't seem to be just that patients are sicker before they develop sepsis.
In a large study of older Medicare enrollees published May 17, 2016, by BMJ, more than one in five sepsis survivors died between a month and two years later as a direct consequence of sepsis.

Late mortality after sepsis “could be more amenable to intervention than previously
thought,” Dr. Prescott and coauthors concluded.

“We will never be able to prevent all sequelae of sepsis, but I do believe
we can reduce the rates of many of these sequelae,” Dr. Prescott said. She
and other experts emphasized the need to diagnose and treat sepsis promptly, identify
and prevent in-hospital complications such as delirium, facilitate early ambulation,
and counsel patients at discharge, as well as screen them for new functional and cognitive
impairments.

The problem of sepsis recovery starts with suboptimal identification and treatment
at onset. “We know we give antibiotics too late, and then don't de-escalate
them enough,” said Theodore Iwashyna, MD, PhD, a medical intensivist and health
services researcher at the University of Michigan and Veterans Health Administration
in Ann Arbor. “Sepsis care is hard, it is often low-tech, and it crosses professions
and hospital divisions. As a result, it often falls through the cracks.”

CMS now requires all hospitals to report on measures for Severe Sepsis and Septic
Shock Management (SEP-1), which went into effect with discharges beginning in October
2015. But the measures require extensive data collection and were recently shown not to measurably improve sepsis survival, according to a review published Feb. 20 by Annals of Internal Medicine (see sidebar).

Postsepsis care in the United States can be even more uneven and is often subpar.
In a recent survey of nearly 1,500 sepsis survivors, most expressed only low to moderate satisfaction with postdischarge support services, researchers reported in a conference abstract published in the December 2016 Critical Care Medicine.

One problem is that sepsis guidelines and studies have tended to focus on short-term
mortality, not cognitive or functional impairment or worsening comorbidities, Dr.
Iwashyna said. “Yet we know half of the 90-day mortality attributable to sepsis
happens after hospital discharge. There are really almost no large randomized trials
that prove that what we do as inpatients or to help patients recover really works
to help them afterwards.”

The handful of randomized trials available has shown mixed results. In a study of
nearly 300 sepsis survivors, tracking postdischarge symptoms and encouraging patients
to engage in physical activity and other self-care measures did not improve mental health compared with usual primary care. These results appeared in the June 28, 2016, JAMA.

What's more, strategies to prevent mortality and long-term impairment don't necessarily
overlap. Among patients with sepsis-associated acute respiratory distress syndrome,
conservative fluid therapy led to fewer ventilator and ICU days but was associated
with a heightened risk of long-term cognitive problems, possibly because of decreased cerebral perfusion, researchers reported in the June
15, 2012, American Journal of Respiratory and Critical Care Medicine.

“As a practicing doctor, here's what I think: Great inpatient care matters,
including prompt recognition [of sepsis], prompt antibiotics, and appropriate resuscitation,”
said Dr. Iwashyna. “Preventing organ failure matters. Getting everybody—whether
on a vent or not—walking to prevent deconditioning matters.” Ventilator
care should emphasize low tidal volumes with minimal sedation, he added. “Make
sure people go home on the right medicines, and not on residual antipsychotics from
their delirium treatment.”

Highly self-motivated patients might be able to follow a structured exercise plan
that increases their activity day by day, but patients who are weaker or who are reluctant
to exercise because of new pain, dyspnea, or limitations are more likely to benefit
from formal rehabilitation—which could be physical therapy, occupational therapy,
pulmonary rehabilitation, or cardiac rehabilitation depending on the situation, Dr.
Prescott said.

Sepsis survivors often face new weakness, fatigue, cognitive impairment, and income
loss. Caregivers also can be inordinately stressed. For these reasons, it's often
best to start with just one or two referrals that cover the worst symptoms, said Dr.
Prescott.

“I think it's important to understand how sepsis fits into a patient's broader
clinical course,” she added. “In a patient with long-standing severe
comorbidities, or progressively declining health status and poor quality of life leading
into sepsis hospitalization, it may be time to discuss a palliative focus. But for
a previously healthy patient who took a big hit during sepsis hospitalization, we
should do everything possible to support their recovery.”

Dr. Iwashyna invests considerable energy in discharge counseling. “I think
you can prevent problems at home by honestly talking with people about the problems
they are likely to have,” he said. “I spend a lot of time talking about
what the weeks going home are going to be like.” He often refers patients to
the Society of Critical Care Medicine's video, “THRIVE: Discharge from the ICU.” “I am also increasingly trying to get people into peer support groups
for ICU and sepsis recovery so they can help each other navigate the pitfalls of our
uncoordinated non-system for care after sepsis,” he said.

Researchers continue to seek mechanisms by which sepsis increases the risk of serious
morbidity and late mortality. But for now, these remain unknown, said Christopher
Sankey, MD, FACP, a hospitalist at Yale School of Medicine in New Haven, Conn.

“Is it related to the site of infection, the kind of bacteria, [or] ICU factors,
such as length of stay or number of procedure? It is likely a combination of all these,
in addition to host factors, including comorbidities and genetic predispositions to
sepsis severity,” he said.

Severity of initial organ dysfunction does not predict later disability or cognitive
impairment, Dr. Iwashyna said. “The organ failures that happen to be hard for
us to manage in inpatients, such as shock and respiratory failure, are not necessarily
the drivers of long-term problems. Instead, keeping infection from progressing to
sepsis by prompt recognition and early antibiotics, early resuscitation is likely
key for everybody. Everybody is at risk of sepsis sequelae.”

Amy Karon is a freelance writer in San Jose, Calif.

Practical tips to prevent, mitigate postsepsis sequelae

Hallie Prescott, MD, MSc, ACP Member, a medical intensivist at the University of Michigan
in Ann Arbor, offered clinicians this advice:

Identify and treat sepsis earlier.

Screen for and work to prevent delirium.

Facilitate early ambulation.

Counsel patients about postsepsis sequelae and risk of recurrent sepsis (e.g., advise
them to watch for confusion, decreased urine output, or clammy skin and to seek medical
care immediately if any of these occur).

Ensure patients are up to date on recommended vaccines to reduce risk of recurrent
infection or sepsis.

At discharge, screen for new functional or cognitive impairments; consider referral
to physical or occupational therapy.

CMS sepsis bundle may not improve survival

The Severe Sepsis and Septic Shock Early Management Bundle (SEP-1), the CMS performance
measure for sepsis care, has no high- or moderate-quality evidence showing that it
improves survival, a recent review found.

Researchers from the National Institutes of Health performed a systematic review and meta-analysis of literature published through Nov. 28, 2017, to evaluate the available evidence on SEP-1 and its
hemodynamic interventions. Randomized and observational studies of deaths in adults
with sepsis who received the SEP-1 bundle or at least one SEP-1 hemodynamic intervention
were considered for analysis. Hemodynamic interventions included serial lactate measurements,
fluid infusion of 30 mL/kg of body weight, and assessment of volume status and tissue
perfusion with focused exam, bedside cardiovascular ultrasonography, or fluid responsiveness
testing. Results were published by Annals of Internal Medicine on Feb. 20.

Twenty studies involving 18 reports met the inclusion criteria. Five articles looked
at serial lactate measurements alone, five articles looked at fluid infusion of 30
mL/kg alone, four articles looked at both serial lactate measurements and fluid infusion,
three articles looked at a component of volume status and tissue perfusion assessment,
and one article looked at all of SEP-1. Lower in-hospital mortality rates after SEP-1
bundle implementation were reported in one single-center observational study. Sixteen
studies, of which two were randomized and 14 were observational, reported an increase
in survival with serial lactate measurements or fluid infusions of 30 mL/kg. All of
the studies had confounders, and none had a low risk of bias. Three randomized trials
found no change in survival with fluid responsiveness testing.

The researchers noted that their review did not include a large number of trials,
that the included studies were of poor quality, and that no studies provided survival
outcomes related to the focused examination or bedside cardiovascular ultrasonography.
However, they concluded that no high- or moderate-level evidence supports the use
of the SEP-1 bundle to improve survival or as a performance measure.

“Similar to other clinicians, we raise concerns that basing hospital accreditation
and reimbursement on use of SEP-1 interventions for all septic patients will transform
unproven practices into universal care and potentially harm patients in whom they
are not indicated,” the authors wrote. “Moreover, requiring use of these
interventions in a CMS performance measure will consume personnel and financial resources
that might be better directed to other, more effective therapies known to be beneficial
and safe in most septic patients.” They called for CMS to examine and improve
its performance measure approval process. The authors of an accompanying editorial said the study should spur a dialogue between CMS and the critical care community to reconsider SEP-1 requirements.

This summary was originally published in the Feb. 28 ACP Hospitalist Weekly.

ACP Hospitalist provides news and information for hospitalists, covering the major issues in the field. All published material, which is covered by copyright, represents the views of the contributor and does not reflect the opinion of the American College of Physicians or any other institution unless clearly stated.